Investigation of the effects of Mianserin on neuropathic pain in rats with streptozotocin-induced diabetes

In this thesis study, effects of subacute administration of mianserin on diabetic hyperalgesia and allodynia, which developed 4 weeks after streptozotocin (STZ) injection, were investigated using several experimental pain-induction methods in rats with diabetes. Effects of mianserin administration on blood glucose levels in rats were assessed by measuring fasting blood glucose levels and conducting the oral glucose tolerance test. Changes in metabolic parameters such as food and water consumption and urine and faeces excretion were observed using a metabolic cage.Administration of mianserin for 7 and 14 days at doses of 30 and 45 mg.kg-1 significantly reduced the high blood glucose levels and improved polydipsia, polyuria, and polyphagia induced by the hyperglycaemic state. With regard to the anti-hyperglycaemic effect, mianserin administered at a dose of 30 mg?kg-1 was found to be as effective as the reference drug metformin (1 g.kg-1).Mianserin administered at doses that induced an anti-hyperglycaemic effect not only showed opioid-mediated acute anti-nociceptive activity but also effectively improved mechanical and thermal hyperalgesia caused by diabetic neuropathy. In addition to having an anti-hyperalgesic effect, mianserin attenuated diabetes-related mechanical and thermal allodynia.To the best of our knowledge, this is the first study to show that the anti-hyperglycaemic and anti-hyperalgesic/anti-allodynic effects of mianserin, an atypical anti-depressant, in the experimental diabetes model were comparable to those of the reference drugs metformin and pregabalin (10 mg.kg-1), respectively. However, the pharmacological mechanisms underlying the anti-hyperglycaemic, anti-hyperalgesic, and anti-allodynic effects of mianserin remain to be elucidated.The results of this thesis study will provide a pre-clinical basis for new approaches of proper drug selection for the treatment of neuropathic pain, which has a high incidence among diabetic patients. Nevertheless, for mianserin to be considered an effective alternative drug for the treatment of diabetic neuropathy, it is necessary to confirm the results of this pre-clinical study in clinical studies.